生物化学：第15章 代谢整合

重庆境内第一座明代壁画古墓惊艳亮相重庆境内第一座明代壁画古墓惊艳亮相v一铲下去一铲下去 精美墓室现身精美墓室现身 v永川青峰镇凌阁堂村2社正在修建一条公路。10日，挖掘机工人陈某像往常一样，挥动机械臂，刨土、装载突然，“轰”的一声，地上冒出一个洞，洞内红光四射！“看起来红彤彤的！大家都惊呆了！”目击村民们说，他们看到这个洞系砖砌，洞口离地5米左右。在洞内发出红光的竟是精美的绘画：一片纯白的洞壁上，祥云、马、鹿、美女姿态万千，栩栩如生。 v村民们还发现洞口放着四只陶制兽，两只陶罐。“这是啥子洞哦？”细心的村民发现两块破碎棺木，才知道这原来是一个墓室！ 五六百年来，她们一直藏身冰冷的黄土下，安静地陪着主五六百年来，她们一直藏身冰冷的黄土下，安静地陪着主人。人。4月月10日，挖掘机一铲下去，她们重见天日：靓丽身日，挖掘机一铲下去，她们重见天日：靓丽身影震惊了现场的工人，引来了数百人围观影震惊了现场的工人，引来了数百人围观 三足人面鸟三足人面鸟昆明滇池爬出昆明滇池爬出10公斤重疑似鳄鱼龟公斤重疑似鳄鱼龟 l鳄龟体型非常大，鳄龟体型非常大，20斤以上斤以上的鳄龟一般都属于成年龟，的鳄龟一般都属于成年龟，年龄一般都在年龄一般都在100岁左右。目岁左右。目前，大鳄龟被列为世界濒危前，大鳄龟被列为世界濒危动物保护红皮书名录中。动物保护红皮书名录中。 l鳄龟平时在水中不好斗，而鳄龟平时在水中不好斗，而在陆上却能猛冲猛咬。指、在陆上却能猛冲猛咬。指、趾具蹼，水栖性，栖息在深趾具蹼，水栖性，栖息在深河、湖泊、泥潭，偶尔接触河、湖泊、泥潭，偶尔接触咸水区域。在人工养殖条件咸水区域。在人工养殖条件下，鳄龟对浅水和深水都有下，鳄龟对浅水和深水都有较好的适应性。鳄龟的食性较好的适应性。鳄龟的食性杂，偏肉食性，主食鱼、虾、杂，偏肉食性，主食鱼、虾、蛙、蝾螈、小蛇、鸭、水鸟，蛙、蝾螈、小蛇、鸭、水鸟，间食水生植物，喜夜间活动、间食水生植物，喜夜间活动、摄食。摄食。 l据了解，据了解，2001年年3月，一只长月，一只长尾巴鹰钩嘴的奇龟曾出现在尾巴鹰钩嘴的奇龟曾出现在滇池岸边。滇池岸边。什么是鳄龟什么是鳄龟 俗名肉龟、小鳄龟、小鳄鱼龟，原产于北美洲和中俗名肉龟、小鳄龟、小鳄鱼龟，原产于北美洲和中美洲。美洲。 鳄龟外形奇特，粗看酷似鳄鱼。头伸出体鳄龟外形奇特，粗看酷似鳄鱼。头伸出体外，不能缩入壳内。上、下颌略尖，背甲较薄，呈外，不能缩入壳内。上、下颌略尖，背甲较薄，呈棕色或棕褐色，中线处有背棱，边缘为齿状；腹甲棕色或棕褐色，中线处有背棱，边缘为齿状；腹甲白色。尾长有肉突，尾前半部背侧有白色。尾长有肉突，尾前半部背侧有1条鳞皮状棱，条鳞皮状棱，并呈锯齿状。鳄龟为淡水栖，肉食为主。并呈锯齿状。鳄龟为淡水栖，肉食为主。 v新华网洛杉矶月日电（记者高原）美国科学家在最新一期美国新华网洛杉矶月日电（记者高原）美国科学家在最新一期美国循循环环杂志网络版上发表研究报告说，妇女腰部脂肪过多对身体危害大，腰杂志网络版上发表研究报告说，妇女腰部脂肪过多对身体危害大，腰部脂肪严重超标可导致妇女过早死亡。部脂肪严重超标可导致妇女过早死亡。 v 这是由哈佛大学、波士顿妇女医院等机构的科学家组成的科研小组在对这是由哈佛大学、波士顿妇女医院等机构的科学家组成的科研小组在对名妇女进行研究后得出的结论。研究发现，名妇女进行研究后得出的结论。研究发现，腰围超过腰围超过 英寸英寸（约厘米）的妇女，她们过早死亡的风险要比腰围在英寸（约（约厘米）的妇女，她们过早死亡的风险要比腰围在英寸（约厘米）以下的妇女高。厘米）以下的妇女高。 v 研究报告说，与腰围在英寸以下的妇女相比，即使腰围超过英研究报告说，与腰围在英寸以下的妇女相比，即使腰围超过英寸的妇女体重正常，她们死于心血管疾病的风险也要高两倍，死于癌症的寸的妇女体重正常，她们死于心血管疾病的风险也要高两倍，死于癌症的风险要高。风险要高。 v 报告说，此前已有研究发现，腰部脂肪过多会增加妇女罹患糖尿病、中报告说，此前已有研究发现，腰部脂肪过多会增加妇女罹患糖尿病、中风和心脏病的风险。风和心脏病的风险。 v 有关专家建议，为了保持身体健康，妇女除了要保持适当的体重外，还有关专家建议，为了保持身体健康，妇女除了要保持适当的体重外，还应注意控制腰部的脂肪。应注意控制腰部的脂肪。宇宙完走参加v20072007年年0404月月1717日日1414時時2929分分v国際宇宙（）滞在米国人女性飛国際宇宙（）滞在米国人女性飛行士行士 （）日、宇宙（）日、宇宙 参加、参加、完走。米航空宇宙局（）非公式記録完走。米航空宇宙局（）非公式記録時間分。宇宙完走史上初時間分。宇宙完走史上初。 昨年昨年 時時間分秒走破、間分秒走破、 参加資格得。参加資格得。主催陸上協会番主催陸上協会番。運動始地球子励。運動始地球子励。 中中 完走完走 飛飛行士、行士、昨年時間分秒走破、血族米研究班分析v2007年04月13日13時02分v米州立大学研究、万年前恐竜骨質抽出分析結果、遺伝的血族当証拠得明。研究論文日付米科学誌掲載。通信伝。 v鳥類恐竜進化上、近関係仮説唱、分子確認初。鳥恐竜進化説補強材料。（時事） 肥満糖尿病発症差異発見英v2007年年04月月13日日12時時23分分v肥満糖尿病関係微妙違（）英肥満糖尿病関係微妙違（）英大見、日付米科学誌（電子版）発表大見、日付米科学誌（電子版）発表。新治療法可能性。新治療法可能性。 v、構成塩基配列所異。国際、構成塩基配列所異。国際協力見万所、糖尿病患者人患者協力見万所、糖尿病患者人患者人頻度差探。人頻度差探。 v結果、患者非患者比、番染色体呼遺伝子、塩結果、患者非患者比、番染色体呼遺伝子、塩基配列所（）（）人割合高基配列所（）（）人割合高。 v父母受継人（研究対象欧州白人約）、父母受継人（研究対象欧州白人約）、人比、糖尿病割以上占型糖尿病約割高。人比、糖尿病割以上占型糖尿病約割高。 v欧州白人約万人対象、体重（）身長（）回割欧州白人約万人対象、体重（）身長（）回割指標使、型糖尿病肥満関係調。人指標使、型糖尿病肥満関係調。人人比、平均体重重、以上肥満約人比、平均体重重、以上肥満約割高。割高。 v欧州父母、双方受継人割程度、日本欧州父母、双方受継人割程度、日本人割程度。遺伝子働。人割程度。遺伝子働。 v板倉光夫板倉光夫 徳島大機能研究長極大規模解析注目。肥満徳島大機能研究長極大規模解析注目。肥満糖尿病仕組解明治療法開発可能性。糖尿病仕組解明治療法開発可能性。 奥运小知识：正常情况下，火炬是不会中途熄灭奥运小知识：正常情况下，火炬是不会中途熄灭v奥运火炬燃烧系统可奥运火炬燃烧系统可抵抗抵抗11级大风和数倍于每小时级大风和数倍于每小时50毫毫米的大雨，米的大雨，所以正常情况下，火炬是不会中途熄灭的。所以正常情况下，火炬是不会中途熄灭的。不过，在历史上火炬有过不过，在历史上火炬有过5次被熄灭的记录，有人曾经次被熄灭的记录，有人曾经拿灭火器熄灭过火炬，也有人不小心把火炬掉在地上导拿灭火器熄灭过火炬，也有人不小心把火炬掉在地上导致火炬熄灭。最有戏剧性的一幕出现在悉尼奥运会的火致火炬熄灭。最有戏剧性的一幕出现在悉尼奥运会的火炬传递过程中，当时有人从火炬手手中抢过火炬扔到海炬传递过程中，当时有人从火炬手手中抢过火炬扔到海里，看看火炬是否会熄灭，可想而知火炬肯定熄灭了。里，看看火炬是否会熄灭，可想而知火炬肯定熄灭了。在这种情况下，工作人员只能拿出在这种情况下，工作人员只能拿出提前准备好的火种罐，提前准备好的火种罐，再次点燃火炬再次点燃火炬。为保持奥运圣火的纯洁性，在整个火炬。为保持奥运圣火的纯洁性，在整个火炬接力中只能使用从奥林匹亚采集来的圣火进行传递。接力中只能使用从奥林匹亚采集来的圣火进行传递。(来来源：现代金报源：现代金报)第十五章第十五章 代谢整合代谢整合代谢的战略代谢的战略主要的代谢途径和控制部位主要的代谢途径和控制部位关键的交叉部位关键的交叉部位代谢调解中重复出现的基本图案代谢调解中重复出现的基本图案主要器官的代谢轮廓主要器官的代谢轮廓Key Termsvallosteric interactionvcovalent modificationvglycolysisvphosphofructokinasevcitric acid cyclevoxidative phosphorylationvpentose phosphate pathwayvgluconeogenesisvglycogen synthesisvglycogen degradationvglucose 6-phosphatevpyruvatevacetyl CoAvketone bodyvstarved-fed cyclevglucose homeostasisvinsulinvglucagonvcaloric homeostasisvleptinvcreatine phosphatevIII. Synthesizing 代谢作用的基本目的是形成代谢作用的基本目的是形成ATP、NADPH、以及合成生物大分子的、以及合成生物大分子的前体前体 ATP是普遍通用货币是普遍通用货币ATP 在肌收缩在肌收缩 主动运输主动运输 信号放大信号放大 生物合成中充当生物合成中充当能源能源燃料分子氧化作用中的共同的燃料分子氧化作用中的共同的中间产物为中间产物为乙酰乙酰CoA多糖类多糖类还原性合成中还原性合成中NADPH是主要的是主要的电子供体电子供体 脂肪合成时加入的二碳单位的酮基脂肪合成时加入的二碳单位的酮基还原成还原成亚甲基是由两分子亚甲基是由两分子NADPH输入四个电子输入四个电子实现的。实现的。 NADPH参与参与 谷氨酸氧化脱氢反应谷氨酸氧化脱氢反应 二磷酸核糖二磷酸核糖脱氧脱氧二磷酸核糖的反应二磷酸核糖的反应 生物分子是从比较小的一套构造生物分子是从比较小的一套构造单元组成的单元组成的葡萄糖葡萄糖淀粉或糖原淀粉或糖原核苷酸核苷酸DNA, RNA氨基酸氨基酸蛋白质蛋白质乙酰乙酰CoA脂肪酸脂肪酸 ，胆固醇等，胆固醇等生成途径和分解途径几乎总生成途径和分解途径几乎总 是不同的是不同的脂肪酸脂肪酸合成和分解合成和分解糖原糖原合成和分解合成和分解核苷酸核苷酸的合成和分解等的合成和分解等糖酵解糖酵解 无氧和有氧条件下无氧和有氧条件下3-磷酸甘油醛脱氢反应磷酸甘油醛脱氢反应 消耗的消耗的NAD+的再生的再生磷酸果糖激酶的调节磷酸果糖激酶的调节 TCA循环循环TCA循环产生一个循环产生一个GTP, 三个三个NADH ， 一个一个FADH2磷酸戊糖途径磷酸戊糖途径目的是合成磷酸戊糖和目的是合成磷酸戊糖和NADPH 高浓度的高浓度的NADPH/NADP+ 和和 NADH/NAD+同时存在使还原性合成反应同时存在使还原性合成反应和糖酵解反应同时进行和糖酵解反应同时进行糖酵解途径与糖异生途径相互抑制糖酵解途径与糖异生途径相互抑制柠檬酸和柠檬酸和ATP激活激活二磷酸果糖酶二磷酸果糖酶 AMP抑制抑制二磷酸果糖酶二磷酸果糖酶柠檬酸和柠檬酸和ATP抑制抑制6-磷酸果糖激酶磷酸果糖激酶 AMP激活激活6-磷酸果糖激酶磷酸果糖激酶二磷酸果糖酶二磷酸果糖酶糖异生的限速酶糖异生的限速酶三个最关键的中间代谢产物三个最关键的中间代谢产物 6-磷酸葡萄糖，磷酸葡萄糖， 丙酮酸，乙酰丙酮酸，乙酰-CoA Key Junctions: Glucose 6-phosphate, Pyruvate, and Acetyl CoA The factors governing the flow of molecules in metabolism can be further understood by examining three importantmolecules: glucose 6-phosphate, pyruvate, and acetyl CoA. Each of these molecules has several contrasting fates:1. Glucose 6-phosphatevGlucose entering a cell is rapidly phosphorylated to glucose 6-phosphate and is subsequently stored as glycogen, degraded to pyruvate, or converted into ribose 5-phosphate (Figure 30.10). Glycogen is formed whenglucose 6-phosphate and ATP are abundant. In contrast, glucose 6-phosphate flows into the glycolytic pathway when ATP or carbon skeletons for biosyntheses are required. Thus, the conversion of glucose 6-phosphate into pyruvate can be anabolic as well as catabolic. The third major fate of glucose 6-phosphate, to flow through the pentose phosphate pathway, provides NADPH for reductive biosyntheses and ribose 5-phosphate for the synthesis of nucleotides. Glucose 6-phosphate can be formed by the mobilization of glycogen or it can be synthesized from pyruvate and glucogenic amino acids by the gluconeogenic pathway.2. Pyruvate.vThis three-carbon a-ketoacid is another major metabolic junction (Figure 30.11). Pyruvate is derived primarily from glucose 6-phosphate, alanine, and lactate. Pyruvate can be reduced to lactate by lactate dehydrogenase to regenerate NAD+. This reaction enables glycolysis to proceed transiently under anaerobic conditions in active tissues such as contracting muscle. The lactate formed in active tissue is subsequently oxidized back to pyruvate, in other tissues. The essence of this interconversion buys time and shifts part of the metabolic burden of active muscle to other tissues. Another readily reversible reaction in the cytosol is the transamination of pyruvate, an a-ketoacid, to alanine, the corresponding amino acid. Conversely, several amino acids can be converted into pyruvate. Thus, transamination is a major link between amino acid and carbohydrate metabolism. A third fate of pyruvate is its carboxylation to oxaloacetate inside mitochondria, the first step in gluconeogenesis. 3. Acetyl CoA.vThe major sources of this activated two-carbon unit are the oxidative decarboxylation of pyruvate and the b-oxidation of fatty acids (see Figure 30.11). Acetyl CoA is also derived from ketogenic amino acids. The fate of acetyl CoA, in contrast with that of many molecules in metabolism, is quite restricted. The acetyl unit can be completely oxidized to CO2 by the citric acid cycle. Alternatively, 3-hydroxy-3-methylglutaryl CoA can be formed from three molecules of acetyl CoA. This six-carbon unit is a precursor of cholesterol and of ketone bodies, which are transport forms of acetyl units released from the liver for use by some peripheral tissues. A third major fate of acetyl CoA is its export to the cytosol in the form of citrate for the synthesis of fatty acids. III. Synthesizing the Molecules of Life 30. The Integration of Metabolism 30.1. Metabolism Consist of Highly Interconnected PathwaysThe Integration of MetabolismWe have been examining the biochemistry of metabolism one pathway at a time, but in living systems many pathways are operating simultaneously. Each pathway must be able to sense the status of the others to function optimally to meet he needs of an organism. How is the intricate network of reactions in metabolism coordinated? This chapter presentssome of the principles underlying the integration of metabolism in mammals. We begin with a recapitulation of thestrategy of metabolism and of recurring motifs in its regulation. We then turn to the interplay of different pathways inregard to the flow of molecules at three key crossroads: glucose 6-phosphate, pyruvate, and acetyl CoA. We consider the differences in the metabolic patterns of the brain, muscle, adipose tissue, kidney, and liver. Finally, we examine how the interplay between these tissues is altered in a variety of metabolic perturbations. These discussions will illustrate how biochemical knowledge illuminates the functioning of the organism. v1. ATP is the universal currency of energy. The high phosphoryl transfer potential of ATP enables it to serve as the energy source in muscle contraction, active transport, signal amplification, and biosyntheses. The hydrolysis of an ATP molecule changes the equilibrium ratio of products to reactants in a coupled reaction by a factor of about 108. Hence, a thermodynamically unfavorable reaction sequence can be made highly favorable by coupling it to the hydrolysis of a sufficient number of ATP molecules.Metabolism Consist of Highly Interconnected Pathways The basic strategy of catabolic metabolism is to form ATP, reducing power, and building blocks for biosyntheses. Let us briefly review these central themes:v2. ATP is generated by the oxidation of fuel molecules such as glucose, fatty acids, and amino acids. The common intermediate in most of these oxidations is acetyl CoA. The carbon atoms of the acetyl unit are completely oxidized to CO2 by the citric acid cycle with the concomitant formation of NADH and FADH2. These electron carriers then transfer their highpotential electrons to the respiratory chain. The subsequent flow of electrons to O2 leads to the pumping ofprotons across the inner mitochondrial membrane . This proton gradient is then used to synthesize ATP. Glycolysis also generates ATP, but the amount formed is much smaller than that in oxidative phosphorylation. The oxidation of glucose to pyruvate yields only 2 molecules of ATP, whereas the complete oxidation of glucose to CO2 yields 30 molecules of ATP.v3. NADPH is the major electron donor in reductive biosyntheses. In most biosyntheses, the products are more reduced than the precursors, and so reductive power is needed as well as ATP. The high-potential electrons required to drive these reactions are usually provided by NADPH. The pentose phosphate pathway supplies much of the required NADPH.v4. Biomolecules are constructed from a small set of building blocks. The highly diverse molecules of life are synthesized from a much smaller number of precursors. The metabolic pathways that generate ATP and NADPH also provide building blocks for the biosynthesis of more-complex molecules. For example, acetyl CoA, the common intermediate in the breakdown of most fuels, supplies a two-carbon unit in a wide variety of biosyntheses, such as those leading to fatty acids, prostaglandins, and cholesterol. Thus, the central metabolic pathways have anabolic as well as catabolic roles.v5. Biosynthetic and degradative pathways are almost always distinct. For example, the pathway for the synthesis of fatty acids is different from that of their degradation. This separation enables both biosynthetic and degradative pathways to be thermodynamically favorable at all times. A biosynthetic pathway is made exergonic by coupling it to the hydrolysis of a sufficient number of ATP molecules. The separation of biosynthetic and degradative pathways contributes greatly to the effectiveness of metabolic control. This reaction and the subsequent conversion of oxaloacetate into phosphoenolpyruvate bypass an irreversible step of glycolysis and hence enable glucose to be synthesized from pyruvate. The carboxylation of pyruvate is also important for replenishing intermediates of the citric acid cycle. Acetyl CoA activates pyruvate carboxylase, enhancing the synthesis of oxaloacetate, when the citric acid cycle is slowed by a paucity of this intermediate. A fourth fate of pyruvate is its oxidative decarboxylation to acetyl CoA. This irreversible reaction inside mitochondria is a decisive reaction in metabolism: it commits the carbon atoms of carbohydrates and amino acids to oxidation by the citric acid cycle or to the synthesis of lipids. The pyruvate dehydrogenase complex, which catalyzes this irreversible funneling, is stringently regulated by multiple allosteric interactions and covalent modifications. Pyruvate is rapidly converted into acetyl CoA only if ATP is needed or if two-carbon fragments are required for the synthesis of lipids.可利用的能量可利用的能量（kcal）葡萄糖或糖原葡萄糖或糖原三酰基甘油三酰基甘油可动员的蛋白质可动员的蛋白质血液血液60450肝肝400450400脑脑800肌肉肌肉1，20045024，000脂肪组织脂肪组织80135，00040表表23-1 典型的体重为典型的体重为70kg的男人的燃料贮存的男人的燃料贮存(P424)大脑，肌肉，脂肪组织，肝的代谢特点大脑，肌肉，脂肪组织，肝的代谢特点表表23-2 饥饿时的燃料代谢饥饿时的燃料代谢(P429)燃料交换和消耗燃料交换和消耗24小时内形成或消耗量（小时内形成或消耗量（g）第第3天天第第40天天脑消耗的燃料脑消耗的燃料葡萄糖葡萄糖100 40酮酮 体体50 100一切其他葡萄糖消耗量一切其他葡萄糖消耗量50 40燃料动员燃料动员脂肪组织的脂解作用脂肪组织的脂解作用180 180肌肉蛋白质降解肌肉蛋白质降解7520肝制造燃料的产量肝制造燃料的产量葡萄糖葡萄糖15080酮体酮体150 150Fuel Choice During Starvation. The plasma levels of fatty acids and ketone bodies increase instarvation, whereas that of glucose decreases肝与肌肉的物质交换肝与肌肉的物质交换葡萄糖葡萄糖-丙氨酸循环丙氨酸循环肌肉蛋白质分解产生的肌肉蛋白质分解产生的丙氨酸丙氨酸由肌肉转运至肝脏由肌肉转运至肝脏糖酵解产生的糖酵解产生的乳酸乳酸由肌肉转运至肝脏由肌肉转运至肝脏丙氨酸丙氨酸，乳酸乳酸在肝中异生为葡萄糖转运至在肝中异生为葡萄糖转运至肌肉肌肉饥饿时的燃料代谢饥饿时的燃料代谢燃料交换和消耗燃料交换和消耗 第三天第三天 第第40天天脑消耗的燃料脑消耗的燃料 （24小时小时/克）克） （24小时小时/克）克） 葡萄糖葡萄糖（酮体酮体） 100（50） 40（100）其他一切葡萄糖耗量其他一切葡萄糖耗量 50 40 脂肪组织脂解作用脂肪组织脂解作用 180 180肌肉蛋白质降解肌肉蛋白质降解 75 25 肝制造燃料的产量肝制造燃料的产量 葡萄糖葡萄糖（酮体酮体） 150（150） 80（150） 典型的体重为典型的体重为70公斤的男人的燃料储公斤的男人的燃料储备（千卡）备（千卡） 葡萄糖葡萄糖 三酰甘油三酰甘油 蛋白质蛋白质 （糖原）（糖原）血液血液 60 45 0肝肝 400 450 400脑脑 8 0 0肌肉肌肉 1200 450 24000脂肪组织脂肪组织 80 135000 40 重复出现的基本图案重复出现的基本图案v变构相互作用变构相互作用v共价修饰共价修饰v酶的水平酶的水平v区域化区域化代谢途径的区域化代谢途径的区域化糖酵解，脂肪酸合成，磷酸戊糖途径在糖酵解，脂肪酸合成，磷酸戊糖途径在胞液中胞液中脂肪酸脂肪酸-氧化，氧化，TCA循环在循环在线粒体线粒体中中尿素合成，糖异生发生尿素合成，糖异生发生在上述两个区域在上述两个区域（开始开始线粒体中，后来在细胞质中线粒体中，后来在细胞质中）思考题；思考题；尿素合成和糖异生的哪几步反应在线粒体中发生？尿素合成和糖异生的哪几步反应在线粒体中发生？Compartmentation of the Major Pathways of Metabolism.)Regulation of Glycolysis. Phosphofructokinase is the key enzyme in the regulation of glycolysis.Regulation of the Pentose Phosphate Pathway. The dehydrogenation of glucose 6-phosphate is thecommitted step in the pentose phosphate pathway.Regulation of Gluconeogenesis. Fructose 1,6-bisphosphatase is the principal enzyme controlling the rateof gluconeogenesis.Control of Fatty Acid Degradation. Malonyl CoA inhibits fatty acid degradation by inhibiting the formation of acyl carnitine.Glycogen Granules. The electron micrograph shows part of a liver cell containing glycogen particles.Courtesy of Dr. George Palade.Metabolic Fates of Glucose 6-Phosphate.Major Metabolic Fates of Pyruvate and Acetyl CoA in Mammals.Each Organ Has a Unique Metabolic ProfilevThe metabolic patterns of the brain, muscle, adipose tissue, kidney, and liver are strikingly different. Let us consider howthese organs differ in their use of fuels to meet their energy needs:1. Brain.vGlucose is virtually the sole fuel for the human brain, except during prolonged starvation. The brain lacks fuel stores and hence requires a continuous supply of glucose. It consumes about 120 g daily, which corresponds to an energyinput of about 420 kcal (1760 kJ), accounting for some 60% of the utilization of glucose by the whole body in the resting state. Much of the energy, estimates suggest from 60% to 70%, is used to power transport mechanisms that maintain the Na+-K+ membrane potential required for the transmission of the nerve impulses. The brain must also synthesize neurotransmitters and their receptors to propagate nerve impulses. Overall, glucose metabolism remains unchanged during mental activity, although local increases are detected when a subject performs certain tasks. Glucose is transported into brain cells by the glucose transporter GLUT3. This transporter has a low value of K M for glucose (1.6 mM), which means that it is saturated under most conditions. Thus, the brain is usually provided with a constant supply of glucose. Noninvasive 13C nuclear magnetic resonance measurements have shown that the concentration of glucose in the brain is about 1 mM when the plasma level is 4.7 mM (84.7 mg/dl), a normal value. Glycolysis slows down when the glucose level approaches the K M value of hexokinase (50 mM), the enzyme that traps glucose in the cell (Section 16.1.1). This danger point is reached when the plasma-glucose level drops below about 2.2 mM (39.6 mg/dl) and thus approaches the K M value of GLUT3. Fatty acids do not serve as fuel for the brain, because they are bound to albumin in plasma and so do not traverse the blood-brain barrier. In starvation, ketone bodies generated by the liver partly replace glucose as fuel for the brain.v1脑 葡萄糖实际上是人脑的唯一燃料，只是在长期饥饿的情况下才有例外。脑没有燃料贮存，因而需要有连续不断的葡萄糖供应，葡萄糖在一切时刻都可以自由地入脑。在饥饿时，酮体（乙酰乙酸及其还原的相应化合物3-羟基丁酸）代替葡萄糖充当脑的燃料。通过CoA从琥珀酰CoA转移使乙酰乙酸活化，产生乙酰乙酸CoA。然后硫解酶使乙酰乙酰CoA断裂，产生两个乙酰CoA分子，后者进入柠檬酸循环。脂肪酸不能充当脑的燃料，因为它们与白蛋白结合，所以不能越过脑血屏障。从本质上看，酮体是可以运输的脂肪酸等效物。 v2. Muscle. The major fuels for muscle are glucose, fatty acids, and ketone bodies. Muscle differs from the brain in having a large store of glycogen (1200 kcal, or 5000 kJ). In fact, about three-fourths of all the glycogen in the body is stored in muscle. This glycogen is readily converted into glucose 6-phosphate for use within muscle cells. Muscle, like the brain, lacks glucose 6-phosphatase, and so it does not export glucose. Rather, muscle retains glucose, its preferred fuel for bursts of activity. In actively contracting skeletal muscle, the rate of glycolysis far exceeds that of the citric acid cycle, and much of the pyruvate formed is reduced to lactate, some of which flows to the liver, where it is converted into glucose. These interchanges, known as the Cori cycle ，shift part of the metabolic burden of muscle to the liver. In addition, a large amount of alanine is formed in active muscle by the transamination of pyruvate. Alanine, like lactate, can be converted into glucose by the liver. Why does the muscle release alanine? Muscle can absorb and transaminate branched-chain amino acids; however, it cannot form urea. Consequently, the nitrogen is released into the blood as alanine. The liver absorbs the alanine, removes the nitrogen for disposal as urea, and processes the pyruvate to glucose or fatty acids. The metabolic pattern of resting muscle is quite different. In resting muscle, fatty acids are the major fuel, meeting 85% of the energy needs. Unlike skeletal muscle, heart muscle functions almost exclusively aerobically, as evidenced by the density of mitochondria in heart muscle. Moreover, the heart has virtually no glycogen reserves. Fatty acids are the hearts main source of fuel, although ketone bodies as well as lactate can serve as fuel for heart muscle. In fact, heart muscle consumes acetoacetate in preference to glucose.v2肌肉 肌肉的主要燃料是葡萄糖、脂肪酸和酮体。肌肉与脑不同，它有大量的糖原贮存（1,200kcal）。事实上，人体内全部糖原约有四分之三贮存于肌肉。这种糖原可以很快地转变为葡糖6-磷酸，供肌肉细胞内使用。肌肉和脑一样地缺乏葡糖6-磷酸酯酶，因而它不向外运输葡萄糖。在活跃地收缩着的骨骼肌内，糖酵解的速度远远超过柠檬酸循环的速度。在这种条件下形成的丙酮酸大部分被还原成乳酸，后者流入肝，并在肝内转变成葡萄糖。这些相互转变称为科里（Cori）循环，可以把肌肉的部分代谢负担转嫁给肝。此外，有大量丙氨酸通过丙酮酸的转氨作用在活跃的肌肉内形成。丙氨酸和乳酸一样，可以被肝转转变为葡萄糖。静止肌肉的代谢情况则很不相同。在静止肌肉内，脂肪酸是主要燃料。酮体也可以充当心肌的燃料。事实上，心肌优先消耗乙酰乙酸，其次才是葡萄糖。v3. Adipose tissue. The triacylglycerols stored in adipose tissue are an enormous reservoir of metabolic fuel In a typical 70-kg man, the 15 kg of triacylglycerols have an energy content of 135,000 kcal (565,000 kJ). Adipose tissue is specialized for the esterification of fatty acids and for their release from triacylglycerols. In human beings, the liver is the major site of fatty acid synthesis. Recall that these fatty acids are esterified in the liver to glycerol phosphate to form triacylglycerol and are tr